FoxO1 signaling as a therapeutic target for type 2 diabetes and obesity

Eur J Pharmacol. 2021 Jan 15:891:173758. doi: 10.1016/j.ejphar.2020.173758. Epub 2020 Nov 27.

Abstract

Glucose production and the consumption of high levels of carbohydrate increase the chance of insulin resistance, especially in cases of obesity. Therefore, maintaining a balanced glucose homeostasis might form a strategy to prevent or cure diabetes and obesity. The activation and inhibition of glucose production is complicated due to the presence of many interfering pathways. These pathways can be viewed at the downstream level because they activate certain transcription factors, which include the Forkhead-O1 (FoxO1). This has been identified as a significant agent in the pancreas, liver, and adipose tissue, which is significant in the regulation of lipids and glucose. The objective of this review is to discuss the intersecting portrayal of FoxO1 and its parallel cross-talk which highlights obesity-induced insulin susceptibility in the discovery of a targeted remedy. The review also analyses current progress and provides a blueprint on therapeutics, small molecules, and extracts/phytochemicals which are explored at the pre-clinical level.

Keywords: FoxO1; Glucose homeostasis; Obesity; Oxidative stress; Therapeutics; Type 2 diabetes.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Obesity Agents / therapeutic use*
  • Biomarkers / blood
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / metabolism
  • Energy Metabolism / drug effects*
  • Forkhead Box Protein O1 / metabolism*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Resistance
  • Lipids / blood*
  • Obesity / complications
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Signal Transduction

Substances

  • Anti-Obesity Agents
  • Biomarkers
  • Blood Glucose
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Hypoglycemic Agents
  • Lipids